Lactones of 2-alkyl-3-alkoxy-4-hydroxymethyl-5-carboxypyridine



r OFFICE.

Eric T. Stiller, New York, N. Y, aslgnoi; to Merck & 00., Inc" Railway, N. 1., a corporation ofNew I Jersey No Drawing. Application December Serial No. 423,136

.10 Claims. (Cl- 260-2975) This invention relates to the lactones of 2-alkyl- 3-alkoxy-4-hydroxymethyl 5 carboxypyridlne,

' andto processes of preparing the same, and is a continuation of our co-pendlng application, Serial No. 267,818, filed April 13, 1939.

An object of the invention is the preparation of the above-mentioned'lactones by simple and economical processes.

I have discovered that the lactones of 2-alkyl- 3-alkoxy-4-'-hydroxymethyl 5 carboxypyridine may be easily prepared in different ways, for example by oxidizing a solution of an alkyl ether of 2-alkyl-3-hydroxy-4,5-dihydroxymethyl pyridine by means of an oxidizing agent, and isolating the lactone formed. The alkyl esters may be prepared according to the process set forth in appligation Serial No. 247,479, filed December 23, 19 8.

The lactones of the present invention may be used for various purposes, for example as intermediates in the manufacture of substances having a biological activity of the type shown by vita- The following examples illustrate methods of carrying out the invention, but it is to be understood that these examples are by way of illustration. and not of limitation.

An aqueous solution of 323 mgs. oi the methyl ether of vitamin B6 are oxidized by slowly adding 27.4'cc. of 0.0947 M barium permanganate, and than allowing the mixture to stand at room temperature for 16 hours. The manganese dioxide formed is removed bycentrifuging and is then thoroughly extracted with warm water. The combined mother liquor and extracts are evaporated at 50 C. under reduced pressure to 50 cc. The barium is quantitatively removed by the additionof N/lil sulfuric acid, and the precipitated barium sulfate is. thoroughly extracted with water. The aqueous solution of theoxidation Products is evaporated to dryness, and submitted to molecular distillation at 10- mm. The crystaltion at 50" C. under reduced pressure to a volume of 1.5 cc. Upon cooling, the lactone crystallizes out. This crystalline material is extracted with ether or benzene, the solvent is evaporated and the lactone recrystallized from water. The crystals are very soluble in alcohols, and sparingly soluble in ether.

Other lactones of 2-alkyl-3-alkoXY-4-hydrol7- methyl-fi-carboxypyridinocan be obtained by a similar method. For example, when starting with dine, the 2-ethyl-3-ethoxy lactone is obtained.

Modifications may be made in carrying out the present invention without departing from the spirit and-scope thereof. For example, oxidizing agents other than barium permanganate may be used.

I claim:

1. A ,lactone of 2-alkyl-3-alkoxy-4-hydroxymethyl-b-carboxypyridine.

2. The lactone of 2-methyl-3-mthoxy-4-hydroxymethyl-5-carboxypyridine.

' duce the lactone or 2-alkyi-3-alkoxy-4-hydroxymethyl-5-carboxy-pyridine and recovering the thus produced lactone.

5. The process comprising oxid'ming a solution of an allryl ether of vitamin Bu by means of barium permanganate to produce the lactone of Z-methyl-3-alkoxy-4-hydroxymethy1-5-carboxy pyridine, and recovering the thus produced lactone.

6. The process comprising oxidizing a solution of the methyl ether of vitamin B6 by means of barium permanganate to produce the lactone of 2-methyl-3-methoxy-4-hydroxymethyl 5 carbo y-Pyridine. and recovering the thus produced lactone.

I. The process comprising oxidizing a solution of 2-ethyl-3-ethoxy-4,5-di-(hydroxymethyl) pyridlne by means of barium permanganate to produce the lacton'e of 2-ethyl-3-ethoxy-4-hydrdxymethyl-o-carboxy-pyridine, and recovering the thus produced lactone. Y

8. The process comprising oxidizing a solution of the methyl ether of vitamin Bu by means of barium permanganate, removing the formed manganese dioxide. treating the solution with sulfuric acid, removing the formed barium sulfate,

and recovering the lactone of 2-methyl-3-methoxy-i-hydroxymethyl-ii-carhoxypyridine.

.9. The process comprising a solution of 2-ethyl-3-ethoxy-L5-di-ihydroxymethyl) pyr- .ldine with barium permanganate, removing the formed manganese dioxide, treating the solution with sulfuric acid, removing the formed barium sulfate, and recoverin the lactone of Z-ethyl- I 3-ethoxy-4-hydroxymethyl-5-carboxypyridine.

V droxymethyl-fi-carboxy-llyridino 10. The process comprisi g a solution of a ,2-aikyl-3-alkoxy-a6-di-(hydroxymethyl) pyridine by means of barium permanganate to produce the lactone of 2-alkyl-3-alkoxy-4-hytemperature. and recovering the time produced lactonc.

' mo '1. M

It ordinary Patent No. 2,5BOA78.

CERTIFICATE m conmzcnou.

ERIC '1'. STILLER.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Page 1, first column, line 15, for the word "esters" read ethers--; and that the said Letters Patent should he read with this correction therein that the same I may conform to the record of the case in the Patent Office.

Signed and sealed this 16th day of October, A. D. 191 5.

Leslie Frazer (Seal) First Assistant Comissioner of Patents. 

